Specialized photoreceptors in the mammalian retina project to the circadian clock of the suprachiasmatic nucleus (SCN). These photoreceptors contain melanopsin. Questions arise regarding the uniqueness of the melanopsin-containing retinal ganglion cell projections to the SCN. Axon collaterals from retinal ganglion cells innervate both the SCN and at least one other visual nucleus. The extent to which the bifurcating ganglion cells contain melanopsin will be addressed. These results have ramifications for the functional studies of the anatomical substrate mediating the temporal integration and photic sensitivity capacity of the circadian rhythm system. Functional experiments are designed to evaluate the role played by various parts in the visual pathway in assessing circadian rhythm system response to light. Drug and lesion experiments will, in sequential fashion, determine whether the pupil, retina, SCN or IGL contribute to the capacity of the hamster circadian rhythm system to effectively assess stimulus brightness or provide stimulus integration over time and generate a rhythm phase shift or induction of FOS protein in nuclei of SCN neurons. For example, animals will receive a unilateral retinal occluder and tested to determine whether functional loss of 50% of the photoreceptors providing information to the circadian clock will modify the magnitude of the phase shift or FOS response to light. Other experiments will determine whether there is a contribution to these responses being made by the SCN or IGL. Part of the logic for studying the latter nucleus rests on the fact that the IGL controls approximately 50% of the circadian period response to constant light. Thus, it may be that the IGL mediates the tonic effects of light (summation of photons across time?), whereas the SCN mediates the phasic effects of light, on the circadian rhythm system. Studies of the retina are directed at the function of the melanopsin-containing retinal ganglion cells. These issues will be studied using dual tract tracing and targeted immunotoxin methods. The overall goal of the project is to further elucidate the contribution of the visual system to the regulation of circadian rhythm response to light with particular emphasis on phase control.